Genetic changes in ATM and ATR/CHEK1 as prognostic indicators in cancer

Abstract

The present invention relates to the discovery that, in human cancer, an 11q deletion of ATM together with an increase in ATR and CHEK1 expression correlates with resistance to ionizing radiation which could be overcome by inhibition of the ATR / CHEK1 pathway. It provides for methods of identifying patients unlikely to exhibit an adequate response to radiation therapy and / or chemotherapy who may benefit from ATR / CHEK1 pathway inhibition, as well as methods of treating said patients.

Description

PRIORITY CLAIM[0001]This application claims priority to U.S. Provisional Application No. 60 / 908,891, filed Mar. 29, 2007; U.S. Provisional Application No. 60 / 912,086, filed Apr. 16, 2007; and U.S. Provisional Application No. 60 / 912,355, filed Apr. 17, 2007, the contents of each of which are incorporated by reference in their entireties herein.GRANT INFORMATION[0002]The subject matter of the present invention was developed, at least in part, under National Institutes of Health Grant No. RO1DE14729, P30CA47904, RO1DE016086, R25CA089507 and P50CA097190, so that the United States Government has certain rights herein.1. INTRODUCTION[0003]The present invention relates to the discovery that, in human cancer, an 11q deletion of ATM together with an increase in ATR and CHEK1 expression correlates with resistance to ionizing radiation which could be overcome by inhibition of the ATR / CHEK1 pathway. It provides for methods of identifying patients unlikely to exhibit an adequate response to radi...

AI Technical Summary

Benefits of technology

"The present invention is about finding a way to treat cancer that is resistant to radiation therapy. The invention is based on the discovery that certain genes are overexpressed in some types of cancer, and that inhibiting those genes can make the cancer cells more susceptible to DNA damage. The invention provides methods for identifying patients who may benefit from treatment with specific inhibitors of those genes. The invention also provides kits for identifying these patients."

Problems solved by technology

Chromosomal segregational defects, involving multipolar spindles are a common cause of numerical chromosomal instability in OSCC (SAUNDERS et al.

Thus, chromosomal instability is a relatively early event in head and neck tumor development.

Thus, perturbation of either ATM or ATR may have a ripple effect and affect the regulation and control of numerous proteins and pathways involved in the DNA damage response.

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